Photoacoustic and ultrasound lung scanning for evaluation of lung injury

ISRCTN	ISRCTN10376207
DOI	https://doi.org/10.1186/ISRCTN10376207
Sponsor	St. Michael's Hospital
Funder	St. Michael’s Hospital Medical Services Association (SMHA) AHSC AFP Innovation Fund Award.

Submission date: 02/09/2026
Registration date: 04/09/2026
Last edited: 04/09/2026

Recruitment status: Recruiting
Overall study status: Ongoing
Condition category: Respiratory

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Pulmonary edema is fluid buildup in the lungs, while pulmonary fibrosis is lung scarring. These conditions can sometimes look similar on standard imaging despite requiring different treatments. PULSE-LI is testing two research imaging methods, quantitative ultrasound and photoacoustic imaging, to develop imaging biomarkers that may help distinguish pulmonary edema from pulmonary fibrosis.

Who can participate?
Adult patients with acute decompensated heart failure and moderate-to-severe pulmonary edema, patients with idiopathic pulmonary fibrosis with a definite usual interstitial pneumonia pattern on computed tomography, and healthy volunteers.

What does the study involve?
Healthy volunteers will attend one imaging visit to help optimize the scanning protocol. Patients will attend one research imaging session using quantitative ultrasound and photoacoustic imaging. Researchers will also collect relevant demographic and clinical information. Patients may separately consent to an optional blood test for N-terminal pro-B-type natriuretic peptide. The research imaging results will not be used for diagnosis or treatment decisions.

What are the possible benefits and risks of participating?
Participants are not expected to receive a direct medical benefit. The study may help develop better bedside imaging methods for lung disease in the future. Risks are expected to be low and may include temporary discomfort from the probe, gel, positioning or protective eyewear. Photoacoustic imaging uses laser light, so protective eyewear is required. Optional blood sampling may cause brief pain, bruising or light-headedness.

Where is the study run from?
St. Michael’s Hospital, Unity Health Toronto, Toronto, Ontario, Canada.

When is the study starting and how long is it expected to run for?
September 2026 to September 2027

Who is funding the study?
The study is investigator-sponsored and supported by the St. Michael’s Hospital Medical Services Association Academic Health Science Centre Alternative Funding Plan Innovation Fund Award.

Who is the main contact?
Dr Alberto Goffi, St. Michael’s Hospital, Unity Health Toronto, alberto.goffi@unityhealth.to.

Contact information

Dr Alberto Goffi
Principal investigator, Scientific, Public

St. Michael's Hospital
30 Bond Street, Donnelly Wing Rm 4-601
Toronto
M5B 1W8
Canada

ORCID ID	0000-0002-9658-3903
Phone	+1 416 864 6060 ext. 2474
Email	alberto.goffi@unityhealth.to

Study information

Primary study design	Observational
Observational study design	Cohort study
Scientific title	Photoacoustic and ultrasound lung scanning for evaluation of lung injury (PULSE-LI): a prospective observational study of healthy adults, adults with acute decompensated heart failure-associated pulmonary edema, and adults with idiopathic pulmonary fibrosis, using quantitative ultrasound and photoacoustic imaging to develop and preliminarily validate structural and functional imaging biomarkers that differentiate pulmonary edema from pulmonary fibrosis
Study acronym	PULSE-LI
Study objectives	Primary Objective: Develop and preliminarily validate QUS- and PAI/MSOT-derived investigational imaging biomarkers capable of differentiating pulmonary edema from pulmonary fibrosis at the bedside. Secondary Objectives: 1. Assess biomarker reproducibility 2. Evaluate the impact of participant characteristics (e.g., skin tone, sex) on imaging performance 3. Explore associations between investigational imaging biomarkers and physiologic, laboratory, and standard imaging parameters
Ethics approval(s)	Submitted 02/09/2026, Unity Health Toronto Research Ethics Board (St. Michael’s Hospital, 30 Bond St, Toronto, M5B 1W8, Canada; +1 416 864 6060 ext. 42557; researchethics@unityhealth.to), ref: 25-131
Health condition(s) or problem(s) studied	Development and validation of novel imaging biomarkers derived from quantitative ultrasound (QUS) and photoacoustic imaging (PAI) to differentiate between pulmonary edema and pulmonary fibrosis.
Methodology	This is a prospective, single-centre observational imaging study conducted in two sequential phases. Participants are not randomized and no treatment is assigned. Participants are enrolled into one of three groups according to their clinical status: healthy adults, adults hospitalized with acute decompensated heart failure and moderate-to-severe pulmonary edema, and adults with idiopathic pulmonary fibrosis and a definite usual interstitial pneumonia pattern on high-resolution computed tomography. In Phase 1, 20 healthy adult volunteers will undergo one research imaging session using quantitative ultrasound and photoacoustic imaging. The thorax will be scanned in protocol-defined anterior, lateral and posterior regions using longitudinal and transverse probe orientations. Quantitative ultrasound images and raw ultrasound radiofrequency data will be acquired, followed by photoacoustic imaging of corresponding thoracic regions. Probe position may be marked on the skin to facilitate spatial alignment between the two imaging techniques. Different acquisition conditions, including tidal breathing versus breath-holding, timing within the respiratory cycle, probe position and insonation angle, will be evaluated to optimize the imaging protocol. Inter- and intra-operator reproducibility will also be assessed. The healthy-volunteer study visit is expected to last no more than 80 minutes, with quantitative ultrasound and photoacoustic scanning each lasting no more than approximately 30 minutes. In Phase 2, 30 patients will be enrolled: 15 with acute decompensated heart failure and moderate-to-severe pulmonary edema and 15 with idiopathic pulmonary fibrosis with a definite usual interstitial pneumonia pattern on high-resolution computed tomography. Each participant will undergo one research imaging session using the quantitative ultrasound and photoacoustic imaging protocol developed in Phase 1. The patient imaging session is expected to last no more than 30 minutes, with approximately 5 minutes of quantitative ultrasound scanning and 5 minutes of photoacoustic imaging. Skin markings may be used to align imaging locations between the two techniques and, where applicable, with computed tomography images. Quantitative ultrasound data will be analysed to develop structural imaging biomarkers related to lung tissue scatterer concentration, size and spacing. Photoacoustic imaging data will be analysed to develop functional and molecular imaging biomarkers related to total haemoglobin concentration/perfusion, oxygen saturation, and water and collagen content. These biomarkers will be compared between healthy, edematous and fibrotic lungs and evaluated for their ability to differentiate pulmonary edema from pulmonary fibrosis. Demographic information including age, sex, weight, height and skin tone will be collected. For patient participants, relevant clinical information will also be obtained from assessments and medical records, including comorbidities, dyspnea and functional classification, pulmonary function tests, six-minute walk testing, chest computed tomography and chest radiography, laboratory investigations, echocardiography, oxygen requirements, oxygen saturation, respiratory rate, blood pressure, heart rate and, where available, arterial blood gas measurements. Patient participants may separately consent to an optional same-day blood sample for N-terminal pro-B-type natriuretic peptide measurement. For hospitalized participants with acute decompensated heart failure, this test will be added to clinically indicated bloodwork whenever feasible to avoid an additional venipuncture. For outpatients with idiopathic pulmonary fibrosis, one study-specific blood sample will be collected at the beginning of the imaging visit. Healthy volunteers will not undergo blood sampling as part of the study. All quantitative ultrasound and photoacoustic imaging measurements are investigational and are collected for research purposes only. They will not be used for clinical diagnosis, monitoring or treatment decisions, and participants will continue to receive their usual clinical care independently of the study imaging results.
Intervention type	Device
Phase	Phase II/III
Drug / device / biological / vaccine name(s)	TUPIL MSOT Acuity Echo
Primary outcome measure(s)	Discrimination between pulmonary edema and pulmonary fibrosis measured using the area under the receiver-operating characteristic curve of a combined classifier derived from quantitative ultrasound structural biomarkers and photoacoustic imaging functional biomarkers at Day 0 (single study imaging visit)
Key secondary outcome measure(s)	Inter-operator reproducibility of quantitative ultrasound and photoacoustic imaging biomarkers measured using intraclass correlation coefficient calculated from biomarker measurements obtained by two operators at Day 0 (single study imaging visit) Intra-operator reproducibility of quantitative ultrasound and photoacoustic imaging biomarkers measured using intraclass correlation coefficient calculated from repeated biomarker measurements obtained by the same operator at Day 0 (single study imaging visit) Association between skin tone and quantitative ultrasound and photoacoustic imaging biomarkers measured using an association between biomarker measurements and skin tone assessed using the Monk Skin Tone Scale at Day 0 (single study imaging visit) Association between investigational imaging biomarkers and clinical and physiological measurements measured using the correlation of quantitative ultrasound and photoacoustic imaging biomarkers with available clinical and physiological measurements, including oxygenation, N-terminal pro-B-type natriuretic peptide concentration and pulmonary function measurements, using Spearman correlation coefficients at Day 0 (single study imaging visit) Differences in quantitative ultrasound and photoacoustic imaging biomarkers among healthy, pulmonary edema and pulmonary fibrosis groups measured using a comparison of biomarker distributions among the three participant groups using analysis of variance or the Kruskal-Wallis test, as appropriate at Day 0 (single study imaging visit)
Completion date	15/09/2027

Eligibility

Participant type(s)
Age group	Mixed
Lower age limit	18 Years
Upper age limit	100 Years
Sex	All
Target sample size at registration	50
Key inclusion criteria	Pulmonary Edema Cohort: Patients hospitalized with acute decompensated heart failure (ADHF) with moderate-to-severe pulmonary edema Pulmonary Fibrosis Cohort: Patients with a diagnosis of IPF with a definite usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT), undergoing outpatient follow-up in pulmonology clinics
Key exclusion criteria	Healthy Volunteers 1. Unable or unwilling to provide informed consent 2. Active smoker, defined as current cigarette smoking or smoking within the past 30 days 3. History of lung or cardiac diseases 4. Tattoos or exogenous pigments within the field of view 5. Pregnancy 6. Photosensitizing medication within 72 hours (e.g., sulfonamides, ampicillin, tetracycline) 7. Current phototherapy 8. History of photosensitive disease, such as porphyria or lupus erythematosus, treatment for a photosensitive disease, or active clinically relevant photosensitivity 9. Open skin lesions/sensitivity in scan field 10. Inability/unwillingness to wear laser safety eyewear 11. Recent use of gas ultrasound contrast agent 12. Inability to tolerate positioning/probe pressure Patients 1. Unable or unwilling to provide informed consent 2. Inability to cooperate with the ultrasound examination (e.g. severe agitation, altered mental status) 3. Invasive mechanical ventilation or non-invasive mechanical ventilation at the time of the study procedure 4. Chronic obstructive pulmonary disease (COPD) 5. Lung emphysema 6. Active malignancy with lung involvement 7. End-stage renal disease requiring renal replacement therapy 8. Recent or active lung infection 9. Acute respiratory distress syndrome (ARDS) 10. Recent thoracic surgery or trauma 11. Active tuberculosis 12. Known history of granulomatous lung disease 13. Active smoking, defined as current cigarette smoking or smoking within the past 30 days 14. Tattoos or exogenous pigments within the field of view 15. Pregnancy 16. Photosensitizing medication within 72 hours (e.g., sulfonamides, ampicillin, tetracycline) 17. Current phototherapy 18. History of photosensitive disease, such as porphyria or lupus erythematosus, treatment for a photosensitive disease, or active clinically relevant photosensitivity 19. Open skin lesions/sensitivity in scan field 20. Inability/unwillingness to wear laser safety eyewear 21. Recent use of gas ultrasound contrast agent 22. Inability to tolerate positioning/probe pressure
Date of first enrolment	15/09/2026
Date of final enrolment	15/06/2027

Locations

Countries of recruitment

Canada

Study participating centre

St. Michael's Hospital

30 Bond Street
Toronto
M5B 1W8
Canada

Results and Publications

Individual participant data (IPD) Intention to share	No

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol file	version 2.1	17/08/2026	04/09/2026	No	No

Additional files

50208_Protocol_v2.1 17Aug2026.pdf: Protocol file

Editorial Notes

04/09/2026: Study’s existence confirmed by the Medical Devices Directorate, Health Canada.